Recent studies in our laboratory have focused on the in vitro generation of human cytotoxic T lymphocytes (CTL) specific for TNP or FITCI modified autologous cells. This system was chosen for three reasons: 1) it represents an in vitro model of the immunobiologic mechanisms involved in the induction, regulation and effector phases of antigen specific human T cell responses; 2) it may have direct clinical relevance to human immunity against virus and tumors; and 3) unlike immune responses to alloantigens, the antigens employed are non-cross reactive, well defined chemical structures. Our initial studies, in short term culture, have defined the phenotype and mechanisms of interactions of distinct T cell subsets involved in the induction and amplication of hapten specific CTL responses. In order to extend these studies, we have recently begun to generate T cell growth factor (TCGF) dependent hapten specific human T cell lines (TCL). TCL cells have been shown to mediate hapten specific cytotoxicity, proliferation and helper activity. Further, these cells can mediate poten suppression. The goal of the present proposal is to employ TCL and clones derived from them to: 1) analyze the fine specificity of the human CTL repertoire; 2) study hapten specific immunoregulatory TCL cells with respect to antigenic stimulus required to trigger regulatory function and the mechanisms by which these activities are mediated; 3) to screen hybridoma monoclonal antibodies in order to further dissect and characterize functionally distinct T cell subsets and 4) to immunize mice for the generation of new monoclonal which may recognize additional differention antigens or, perhaps, the T cell receptor.